2, 3‐Dihydroxy‐quinoxaline induces ATPase activity of Herpes Simplex Virus thymidine kinase. Issue 3 (25th December 2013)

• Record Type: Journal Article
• Authors: Zeifman, Alexey A.; Novikov, Fedor N.; Stroylov, Victor S.; Stroganov, Oleg V.; Chilov, Ghermes G.; Skoblov, Alexander Y.; Miroshnikov, Anatoly I.; Skoblov, Yuri S.
• Is Part Of: FEBS letters. Volume 588:Issue 3(2014)
• Page Start: 509
• Page End: 511
• Publication Date: 2013-12-25
• Subjects: DHQ -- 2, 3-dihydroxy-quinoxaline -- HSV-TK -- Herpes Simplex Virus thymidine kinase -- TLC -- thin layer chromatography -- Enzyme kinetic -- Inhibition -- Molecular docking -- Thymidine kinase; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2013.12.017
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 2, 3‐Dihydroxy‐quinoxaline, a small molecule that promotes ATPase catalytic activity of Herpes Simplex Virus thymidine kinase (HSV‐TK), was identified by virtual screening. This compound competitively inhibited HSV‐TK catalyzed phosphorylation of acyclovir with K i = 250 μM (95% CI: 106–405 μM) and dose‐dependently increased the rate of the ATP hydrolysis with K M = 112 μM (95% CI: 28–195 μM). The kinetic scheme consistent with this experimental data is proposed. Abstract : 2, 3‐Dihydroxy‐quinoxaline inhibits acyclovir phosphorylation by herpesvirus thymidine kinase. 2, 3‐Dihydroxy‐quinoxaline promotes ATPase activity of herpesvirus thymidine kinase. This promotion is dose‐dependent and follows the Michaelis–Menten scheme. We propose a kinetic scheme for the whole process that is consistent with the experimental data.